It has long been known that there is some degree of localisation
of function in the human brain, as indicated by the effects of
traumatic head injury. Work in the middle of the 20th century,
notably the direct cortical stimulation of patients during
neurosurgery, suggested that the degree and specificity of such
localisation of function were far greater than had earlier been
imagined. One problem with the data based on lesions and direct
stimulation was that the work depended on the study of what were,
by definition, damaged brains. During the second half of the 20th
century, a collection of relatively non-invasive tools for
assessing and localising human brain function in healthy
volunteers has led to an explosion of research in what is often
termed “Brain Mapping”. The present article reviews some of the
history associated with these tools, but emphasises the current
state of development with speculation about the future. (C) 2001
Elsevier Science B.V. All rights reserved.

Savoy, 2001 page 28

There is no shortage of things to be worried about in the domain
of functional brain mapping. The theme of this section will be
a collection of related concerns that all stem from the limitations
of reporting data as a collection of activated voxels. The
variations on this theme concern "thresholds", the consequences of
increasing statistical power of the tools, and the interpretation
of the "most active" voxels across a small set of stimulus
classes.

Consider, first, the question of thresholds. In a typical block
design fMRI or PET experiment the data collected during one type of
block are compared to the data collected during another type of
block. A statistical test is applied at each voxel in space to
decide when the difference between the distributions collected
during the two types of blocks are statistically significant. A
"map" is presented, typically showing anatomy in the background,
with a coloured overlay indicating those voxels for which the
statistic exceeds some threshold. How is that threshold
determined?

Savoy, 2001 top of page 30

This problem is likened to the classic question raised by
Paul Meehl in the context of general experimental questions in
psychology. Meehl's observation was simply that if psychological
questions take the form "Will Group A differ from Group B by
scoring statistically differently (either higher or lower) on some
behavioural measure X"?, then as we increase the power of our
statistical tests, the answer will almost certainly be Yes, for
any A, B, and X! That is, while correlation
between two presumptively equivalent groups on an unrelated task
(e.g., Group A ¯ persons with red hair; Group B ¯ persons with
brown hair; and the task X is IQ score) is likely to be
insignificant when the number of subjects is modest (say,
N=20 in each group), the story changes when N=55,000.
The reason is simply that even hair colour has some association
with ethnicity, which might be associated with religious
orientation, which might be associated with emphasis on education,
etc. The associations are weak enough that they do not yield a
significant relationship between the groups and the task when
N is small, but they do when N is large. As a
dramatic demonstration of this point, Meehl cites a study of 55,000
Minnesota high school seniors, for whom statistically significant
correlations were found in 91% of pairwise comparisons among
miscellaneous measures such as sex, college choice, club
membership, mother's education, dancing, interest in woodworking,
birth order, religious preference, number of siblings, etc. These
were not "spurious" correlations, but real associations that were
detected because of the form of the question and the power of the
test made possible by a very large N.

Savoy 2001, bottom of page 30

It is believed that there is a highly analogous problem lurking
in the context of functional neuroimaging.

The analogous concern applies to questions of the form, “Will area
A in the cortex show a change in activity (an increase or decrease)
in response to task X, compared to its response to task Y?”;

If our imaging system is powerful enough;

if we design more effective receiver coils for the MR scanner;

if we use more subjects;

if we collect data for a longer period of time),

then the answer will almost always be Yes, for any A, X, and Y.

Once we get past the peripheral sensory systems (i.e., once we have
reached the thalamus), there are only about 5 synapses between any
two neurones in the brain.

It is likely that the activity in any one neurone (or collection
of neurones, given the spatial resolution of our non-invasive
imaging techniques) is going to influence almost any other
neurone,albeit weakly.

Data collected across multiple subjects on the same task give a
hint of such a conclusion, in that the apparent area of activation
increases as the number of subjects increases, as long as the
threshold for statistical significance is held constant.

Savoy, 2001, page 10

It is important to note that the enterprise of brain mapping did
not begin with fMRI or any other non-invasive imaging tool. The
understanding that localisation of function is pervasive in the
human brain has been well established for more than 50 years.
Consider, for example, the summary of this knowledge represented by
Fig. 1, reproduced from a book published in 1957 (Polyak,
1957). There are at least two kinds of questions that should be
asked about this figure. The first questions are methodological:
What is the basis for this figure? Where did the data come from?
What were the technologies that gave rise to this data? The answer
to these first questions is that the figure is based upon two
techniques: study of people with lesions (caused, for example, by
stroke, disease or traumatic wounds) and the direct electrical
stimulation of the cortex of patients undergoing brain surgery.
More about these techniques will be written below.

Fig. 1. This figure schematically summarises the state of
knowledge of localisation of human functional brain in
1957. It is based on data from lesions and studies using
direct cortical stimulation during neurosurgery.
(Reproduced with permission from the publisher from Fig.
#275, p. 456 of "The Vertebrate Visual System", by
Stephen Polyak).

Thus, Fig. 1 teaches us that we were far from ignorant or
misguided about localisation of brain function in 1957. So, what is
all the current excitement about? The primary answer1 is
that today there are a host of technologies that can be used to
give us information non-invasively that address the same issue. The
study of patients with lesions, or those who are undergoing direct
cortical stimulation during surgery, has substantial limitations.
For ethical reasons, neither lesions (obviously) nor direct
electrical stimulation of the brain via surgery (for reasons of
general risk associated with exposing the brain) may be used in the
study of healthy human subjects